Genetic Variant NM_018971.3:c.20C>G (chr3-71754069-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_018971.3(GPR27):c.20C>G(p.Pro7Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000867 in 1,152,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P7L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.7e-7 ( 0 hom. )

Consequence

GPR27
NM_018971.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.625

Publications

0 publications found

Variant links:

Genes affected

GPR27 (HGNC:4482): (G protein-coupled receptor 27) GPR27 is a member of the G protein-coupled receptors (GPCRs), a large family of receptors that have a similar structure characterized by 7 transmembrane domains. Activation of GPCRs by extracellular stimuli such as neurotransmitters, hormones, or light induces an intracellular signaling cascade mediated by heterotrimeric GTP-binding proteins, or G proteins.[supplied by OMIM, May 2010]

GPR27 links:

ENSG00000285708 (HGNC:):

ENSG00000285708 links:

EIF4E3 (HGNC:31837): (eukaryotic translation initiation factor 4E family member 3) EIF4E3 belongs to the EIF4E family of translational initiation factors that interact with the 5-prime cap structure of mRNA and recruit mRNA to the ribosome (Joshi et al., 2004 [PubMed 15153109]).[supplied by OMIM, Mar 2008]

EIF4E3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06425297).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018971.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR27	NM_018971.3	MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 1	NP_061844.1	F1DAM3
EIF4E3	NM_001134649.3		c.-291+146G>C		intron	N/A	NP_001128121.1	Q8N5X7-2
EIF4E3	NM_173359.5		c.-291+575G>C		intron	N/A	NP_775495.1	Q8N5X7-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GPR27	ENST00000304411.3	TSL:6 MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 1	ENSP00000303149.2	Q9NS67
ENSG00000285708	ENST00000647725.1		c.-959+146G>C		intron	N/A	ENSP00000497585.1
EIF4E3	ENST00000421769.6	TSL:1	c.-291+575G>C		intron	N/A	ENSP00000411762.2	Q8N5X7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.67e-7

AC:

AN:

1152960

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

567114

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22294

American (AMR)

AF:

0.00

AC:

AN:

15896

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15584

East Asian (EAS)

AF:

0.00

AC:

AN:

21252

South Asian (SAS)

AF:

0.00

AC:

AN:

58924

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26004

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3004

European-Non Finnish (NFE)

AF:

0.00000106

AC:

AN:

946498

Other (OTH)

AF:

0.00

AC:

AN:

43504

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.024

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.51

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.064

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

0.63

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.75

REVEL

Benign

0.015

Sift

Uncertain

0.024

Sift4G

Benign

0.23

Polyphen

0.15

Vest4

0.068

MutPred

0.23

Loss of glycosylation at P7 (P = 0.0412)

MVP

0.043

ClinPred

0.054

GERP RS

0.87

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.093

gMVP

0.056

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over